Studies on the mechanisms of toxins have continued. Most of the modified toxins appear to lose their biological activity on whole cells as well as on the intact animal, yet the A-chain remains still active in inhibiting protein synthesis on the in vitro ribosomal system. Our results suggest that the cells are able to bind the modified toxin almost identically as with the native toxins, but they are not internalized into the cell. We are continuing studies to determine where in the internalization process the specificity for the intact toxin is required. We have found that polylysine is a good carrier for drugs in promoting cytotoxicity. We have found that at high concentrations the polylysines, particularly of high molecular weight, are cytotoxic. We are now involved in attempting to understand the mechanisms of how polylysine exerts cytotoxicity. Evidence supports ours and others view that the polylysine can be internalized by cells. Studies have been continued on the structure of NAD analogues and some evidence has been gathered with respect to the nature of conformation of the pyridine nucleotide analogue and its activity. Studies also have been carried out on the potentiality of the nude mouse to form antibodies. Our results indicate that there is some capacity of nude mouse spleen cells to activate precursor T-cells when proper stimuli are present. The nature of these stimuli is now being investigated and it is hoped that some clue will be given as to the mechanism of control by which the lymphocytes are matured in the intact animal.